PUBLICATION
Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
- Authors
- Tokunaga, Y., Shirouzu, M., Sugahara, R., Yoshiura, Y., Kiryu, I., Ototake, M., Nagasawa, T., Somamoto, T., Nakao, M.
- ID
- ZDB-PUB-170810-6
- Date
- 2017
- Source
- Scientific Reports 7: 7536 (Journal)
- Registered Authors
- Keywords
- Innate immunity, Innate lymphoid cells, VDJ recombination
- MeSH Terms
-
- Adaptive Immunity/genetics
- Adaptive Immunity/immunology*
- Animals
- B-Lymphocytes/immunology*
- B-Lymphocytes/metabolism
- Disease Resistance/genetics
- Disease Resistance/immunology
- Fish Diseases/genetics
- Fish Diseases/immunology
- Fish Diseases/virology
- Hepatopancreas/immunology
- Hepatopancreas/metabolism
- Homeodomain Proteins/genetics
- Homeodomain Proteins/immunology*
- Homeodomain Proteins/metabolism
- Homeostasis/genetics
- Homeostasis/immunology
- Humans
- Immunity, Innate/genetics
- Immunity, Innate/immunology*
- Mice
- Spleen/immunology
- Spleen/metabolism
- T-Lymphocytes/immunology*
- T-Lymphocytes/metabolism
- Zebrafish/genetics
- Zebrafish/immunology*
- Zebrafish/metabolism
- PubMed
- 28790360 Full text @ Sci. Rep.
Citation
Tokunaga, Y., Shirouzu, M., Sugahara, R., Yoshiura, Y., Kiryu, I., Ototake, M., Nagasawa, T., Somamoto, T., Nakao, M. (2017) Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts. Scientific Reports. 7:7536.
Abstract
rag1 -/- zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 -/- zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels. Our developed microscale assays provided evidence that rag1 -/- fish do not possess serum IgM protein, that they do not achieve specific protection even after vaccination, and that they cannot induce antigen-specific CTL activity. The mortality rate in non-vaccinated fish suggests that rag1 -/- fish possess innate protection equivalent to that of rag1 +/- fish. Furthermore, poly(I:C)-induced immune responses revealed that the organ that controls anti-viral immunity is shifted from the spleen to the hepatopancreas due to the absence of T- and B-cell function, implying that immune homeostasis may change to an underside mode in rag-null fish. These findings suggest that the teleost relies heavily on innate immunity. Thus, this model could better highlight innate immunity in animals that lack adaptive immunity than mouse models.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping